End Stage Renal Disease (ESRD) is associated with an accumulation of "uremic" toxins in essentially three categories: small water-soluble compounds, larger middle molecules, and small protein bound molecules. Current treatment modalities do not address the removal of small protein-bound substances. This research targets an ionic-hemodiafiltration-based product that removes small protein-bound solutes from blood; this function is not addressed by existing technology. This can be an extension of our unique multistage diafiltration process, with two diafiltration steps in series and substitution fluid added in a middilution mode (US Patent #6303036); or can be integrated with standard dialysis technology. An agent is added to dialysate fluid entering a first stage, causing an ionic (pH) shift of the blood, thereby dissociating a significant portion of protein-bound toxins from their conjugated protein counterparts. Once unbound, the small toxins are transported across a semi-permeable membrane by diffusive/convective mechanisms. A second stage acts to return the ionic-altered blood to a normal condition before reinfusion. This Phase I research will qualify agents to be added to the dialysate fluid entering the first stage, so as to ensure safety and efficacy. [unreadable] [unreadable] PROPOSED COMMERCIAL APPLICATION: As of 2001, there were over 300,000 ESRD patients in the US, served by over 60,000 dialysis machines; this market is expected to exceed $500 million annually by 2008. Incorporating ionic technology will provide the unique benefit of removing protein-bound toxins, thereby reducing various comorbid conditions associated with toxic accumulation, improving overall patient health, and reducing associated hospitalizations, currently representing a $600 million+ annual expenditure. Additional applications include treatment of patients intoxicated with poisons or drugs with known protein binding characteristics.